BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Sinusitis is a prevalent nasal disease in children, characterized by chronic and difficult-to-treat symptoms. Its onset is related to nasal stagnation, gallbladder and lung dysfunctions. This article explores the root cause based on Huangdi Neijing by considering the physiological and pathological characteristics of children. The core pathogenesis of pediatric sinusitis is the transmission of heat from the gallbladder and lung to the brain and nose, disrupting normal nasal function. Wind and heat pathogens often persist, accumulate, and transform into turbid qi, which are common triggers of the disease. Evil qi retention and yin depletion are internal factors that cause the prolonged and unhealed condition of the disease. This article emphasizes individualized treatment approaches based on disease duration and the severity of pathogenic factors. If external pathogens remain uncleared, treatment should focus on dispelling wind, clearing heat, dispersing with pungent medicinals, and dredging nasal orifices. If internal fire is exuberant, clearing lung qi, inhibiting hyperactive liver yang, and clearing exuberant fire should be used to relieve stagnation. In chronic cases with residual pathogens and liver-kidney yin deficiency, nourishing yin, clearing fire, and moistening the nasal orifices are essential. When exuberant heat has subsided, but the symptom of a persistent runny nose continues, leading to the loss of healthy qi and damage to the lung and spleen, treatments that tonify the spleen, benefit the lung, and reinforce healthy qi should be adopted to relieve stagnation. These treatments aim to restore the balance of the body′s vital qi by addressing both the lingering symptoms and the underlying weakness of the lung and spleen. The diagnosis and treatment of pediatric sinusitis based on the theory of "the transmission of heat from gallbladder and lung" can help reduce the recurrence of sinusitis and alleviate symptoms, with the aim of broadening the approach of traditional Chinese medicine in treating this condition.

Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Objective:To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.Methods:Two patients treated at the Children′s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). This study was approved by the Children′s Hospital of Henan Province (Ethics No. 2023-K-075).Results:Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.21q22.1)[40]/46, XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11.21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them.Conclusion:Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

Objective:To investigate pathological features and differential diagnosis in the gonads with disorder of sex development.Methods:Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People′s Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed.Results:Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT.Conclusions:Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

Objective:To investigate the correlation between clinical phenotypes and genetic characteristics of children with ring chromosomes (RCs).Methods:Case series study.The clinical data of 11 434 children who received treatment and peripheral blood chromosome karyotype detection in Henan Children′s Hospital from October 2008 to October 2023 due to growth retardation, intellectual impairment or congenital malformation were analyzed retrospectively.A total of 25 children with RCs were selected.Their age at diagnosis, karyotype distribution, clinical manifestations, and genetic detection results were analyzed.Results:RCs were detected in 25 out of 11 434 children, with a detection rate of 0.21%.The genome-wide copy number variation (CNV) analysis was performed on 7 RCs cases, and it found that pathogenic variation existed in all of them.Among the 25 RC cases (11 males and 14 females of social gender), the age at diagnosis ranged from 2 months to 14 years; there were 20 autosomal rings and 5 sex chromosome rings; 13 cases had chimeric karyotypes, and 12 cases had non-chimeric karyotypes.Most of the 25 children showed clinical manifestations of mental or developmental retardation, and some also presented with specific clinical manifestations, such as short stature, congenital malformation, and epilepsy.Conclusions:The pathogenesis of RCs is complex.The clinical manifestations are determined by both RCs syndrome and specific phenotypes caused by the dose effect and exhibit high heterogeneity, so it is easy to miss or misdiagnose.The combined application of cellular and molecular genetic detection technology can facilitate early diagnosis and treatment of RCs, and the correlation analysis of phenotypes and genetic characteristics can provide guidance for genetic counseling.